Negative Serology by Immunoenzymatic Test (EIA) in HIV-infected Children Treated Early With Antiretroviral in the ANRS-Pediacam Study: Pathophysiological Mechanisms

There will be two phases of the study :

* A retrospective phase: case-control study The analyzed data are those collected previously or measured from the already available bio bank, within the framework of the Pediacam III cohort during the primary infection phase before the initiation of HAART, at 6 months after the end of the first series of EPI vaccines, and at 2 years.
* A prospective phase: cross-sectional study Based on an ad hoc bio bank created for parameters we couldn't measure on the existing bio bank

• Blood sampling (Biological): Blood samples collected from children followed in the Pediacam III ANRS12225 cohort

Primary outcomes

• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of sCD14 (µg/ml). Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of BAFF using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of CXCL13 using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of TNF-α (pg/ml). Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of IL-10 (pg/ml). Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of IP-10 (pg/ml). Levels of these biomarkers will be compared across all groups.
• Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma [18 months]: Measure of TRAIL (ng/ml). Levels of these biomarkers will be compared across all groups

Secondary outcomes

• - Humoral response to vaccines against tetanus, pertussis, and viral hepatitis B [18 months]: Serum concentrations of human IgG antibodies against tetanus-toxoid, pertussis, and viral hepatitis B will be measured using commercially available ELISA quantification kits and results will be given as IU/mL
• - Functional and phenotypic characterization of B and T lymphocytes [18 months]: Level (cells/μL or percentage) of T and B-cell lymphocytes subpopulations will be assess in blood using flow cytometry. Functional characterization of T and B lymphocytes will be done by cell culture following by cytokine production titration
• - Size of the HIV reservoir [18 months]: Measure total (copies/million PBMC), integrated (copies/million PBMC), unintegrated (copies/million PBMC) HIV DNA level in Peripheral Blood Mononuclear Cells (PBMC)
• - Residual viremia in perinatally HIV-infected adolescent [18 months]: Any detectable HIV-RNA below 50 copies/mL
• - Level of HIV plasma p24 [18 months]: Measure plasma level of HIV p24 antigen (fg/ml) using ultrasentsitive technique called Simoa (Single molecule array)
• - HLA phenotype and the KIR genotypes [18 months]: HLA-B (27 et 57), HLA-B35 ou 53, HLA-C16:01+KIR2DL3+

Sex: All, accepts healthy volunteers

Inclusion Criteria:

Case control study

* Children included and followed in the ANRS 12225 study - Pediacam III
* Having plasma samples in the bio bank during the above-mentioned periods Case:children with at least one negative HIV serology made by ELISA, permanent or transientduring follow-up.

Control (4 groups)

* HIV-infected children with positive serology and viral load (VL) <400 copies /ml
* HIV-infected children with positive serology and VL ≥400 copies / ml
* HIV-uninfected children born to HIV-positive mothers
* HIV-uninfected children born to HIV-uninfected mothers Selection of cases and controls will be matched on gestational age (premature <37, term ≥37 weeks) and year of birth (2007-2008 and 2009-2010).

Cross sectional study Inclusion criteria

* All children still followed in the ANRS - Pediacam III cohort
* Written consent of one of the parents or the guardian and assent of the child if aged ≥ 11 years and complete disclosure of HIV statusfor infected children for participation to the study.

Exclusion Criteria:

* Refusal by one of the parents or the guardian for the child's participation in the study
* No assent of the child (if aged ≥ 11 years and with complete disclosure of HIV status, for infected children)